Hepatic steatosis is characterized by the accumulation of lipid droplets (LDs), which are composed of a neutral
lipid core surrounded by a
phospholipid monolayer embedded with many
proteins. Although the LD-associated
proteome has been investigated in multiple tissues and organisms, the dynamic changes in the murine LD-associated
proteome in response to
obesity and hepatic steatosis have not been studied. We characterized the hepatic LD-associated
proteome of C57BL/6J male mouse livers following high-fat feeding using isobaric tagging for relative and absolute quantification. Of the 1,520
proteins identified with a 5% local false discovery rate, we report a total of 48
proteins that were increased and 52
proteins that were decreased on LDs in response to high-fat feeding. Most notably, ribosomal and endoplasmic reticulum
proteins were increased and extracellular and cytosolic
proteins were decreased in response to high-fat feeding. Additionally, many
proteins involved in
fatty acid catabolism or
xenobiotic metabolism were enriched in the LD fraction following high-fat feeding. In contrast,
proteins involved in
glucose metabolism and
liver X receptor or
retinoid X receptor activation were decreased on LDs of high-fat-fed mice. This study provides insights into unique
biological functions of hepatic LDs under normal and steatotic conditions.